A concentration measuring device is known, which is capable of measuring a concentration of a blood component such as grape sugar (glucose) and the like with an electrode type sensor based on the enzyme electrode method by supplying one drop of blood to a small region for receiving a sample liquid called a “spot-application region”. The spot-application region is a target area for a user to drop a sample liquid to such as blood and the like, and also a receiving port of a sample liquid for a concentration measuring device.
In a conventionally known concentration measuring device (e.g., design registration No. 1222931 “liquid component concentration meter” and the like), generally, a case opening is formed on an upper surface of the body (case or housing) of a device, and a spot-application region for receiving a sample liquid is provided at the center in the case opening. The spot-application region is a small circular region having a diameter of about 3 mm-4 mm. One drop of the collected blood is dropped on the spot-application region (generally about 5-20 μL (microliter)), and a measurement starting switch is switched on, and then the concentration of the object component in the blood is measured by an electrode type sensor (also called enzyme electrode and the like) inside the device.
FIGS. 7A and 7B are cross-sectional views showing an example manner to measure, by an electrode type sensor, the concentration of the components in the blood dropped on the spot-application region of the above-mentioned concentration measuring device.
As shown in FIG. 7A, a case opening 110 is formed at a predetermined position of a case 100 of the concentration measuring device. A belt-shaped film 120 having spot-application regions at given intervals is set right beneath the case opening 110. When a user looks into the case opening from the outside, the main surface of the film is seen. In this constitution, the film 120 is intermittently fed from a delivery roll (not shown) to a winding roll (not shown) by a constant length such that a new spot-application region is positioned at the center in the case opening 110 for each measurement. The film 120 (whole film including delivery roll and winding roll) is provided as a replaceable cartridge.
The film 120 has a two-layer structure comprising a supporting film 121 as an upper layer and a blood cell separating membrane 122 as a lower layer. The blood cell separating membrane 122 is one kind of a filter membrane having many minute holes through which only the blood plasma can penetrate.
In the supporting film 121, through holes 130 having a diameter of about 3-4 mm to be the opening of the spot-application region are formed at a predetermined space in the longitudinal direction (feeding direction), and a blood cell separating membrane 122 is exposed on the bottom of each through hole. The through holes 130 and the blood cell separating membrane 122 on the inner bottom surface constitute the spot-application region. When blood is dropped in the through hole, the plasma in the blood penetrates the blood cell separating membrane and oozes out on the undersurface of the film.
As shown in FIG. 7A, sample blood X10 is dropped on the through hole 130 which is a spot-application region from an injection syringe, a micropipette 200 or the like, and when the measurement starting switch is switched on, the belt-shaped film 120 is horizontally fed by a predetermined length and stops as shown in FIG. 7B. Then, an electrode type sensor 140 ascends from below the through hole 130 and the top surface thereof (projected to form a spherical surface in preferable embodiment) comes into contact with the undersurface of the blood cell separating membrane 122 where the blood plasma has oozed out, whereby the top surface of the electrode type sensor 140 contacts the blood plasma. In FIGS. 7A and B, the magnitude correlation between the through hole and the electrode type sensor, and the ratio of layer thickness of respective layers are ignored and the structure is exaggeratingly depicted for the sake of explanation.
The outline of the principle of the concentration measurement by the above-mentioned electrode type sensor 140 is as follows in an example of the concentration measurement of blood glucose based on the hydrogen peroxide electrode method which is one kind of the enzyme electrode methods.
(A) Blood plasma that penetrated the blood cell separating membrane 121 contacts the top part of the electrode type sensor 140.
(B) grape sugar contained in the blood plasma passes through a cap film 141 formed as a surface layer of the electrode type sensor 140. The cap film 141 has a tree-layer structure (diffusion limiting film as surface layer, grape sugar oxidize immobilizing film as middle layer, hydrogen peroxide selective permeable film as under layer), and covers the upper surface of a hydrogen peroxide electrode 142 which is the main body of the sensor.
(C) When grape sugar passes through the cap film 141, it is decomposed by a catalytic action of an enzyme in the cap film middle layer to produce gluconic acid and hydrogen peroxide, and hydrogen peroxide penetrates a hydrogen peroxide selective permeable film of the cap film under layer to reach a hydrogen peroxide electrode. The hydrogen peroxide electrode 142 has a concentric cylinder-shaped structure, wherein a working electrode (anode, Pt) is provided in the central part. On the outer side thereof, a reference electrode (AgCl) is provided via an insulating layer. Then, on the outer side thereof, a counter electrode (cathode, Ag) is provided via an insulating layer.
The electrode type sensor (enzyme electrode) is explained in detail in, for example, JP-A-H4-34354 “ENZYME ELECTRODE”, JP-A-H9-119914 “BIOSENSOR”, JP-A-2006-126046 “WASHING TREATMENT METHOD OF ELECTRODE TYPE SENSOR, WASHING TREATMENT MECHANISM AND CONCENTRATION MEASURING INSTRUMENT EQUIPPED WITH THE MECHANISM” and the like. In addition, the mechanism for setting the above-mentioned film as a replaceable cartridge is explained in detail in, for example, JP-A-H4-230840 “CONCENTRATION MEASURING DEVICE” and the like.
In a concentration measuring device as mentioned above, for example, when grape sugar is the measurement target, it is recommended to use an aqueous grape sugar solution having a known concentration (standard concentration test solution) as a sample liquid for calibration and, for initial sensitivity adjustment and periodic sensitivity modification, drop the standard concentration test solution into a spot-application region, and adjust the indicated values on the concentration measuring device to be appropriate.
The concentration measuring device as mentioned above can measure the concentration of the object component by simply receiving a drop of a sample liquid from an injection syringe, a micropipette or the like.
However, the present inventors have detailedly studied the operability of a concentration measuring device as mentioned above, and found that a small amount (one drop) of a sample liquid causes the following problem.
That is, a spot-applying operation including dropping a recommended suitable amount of blood on a spot-application region and entirely covering the blood cell separating membrane exposed in the spot-application region with the sample liquid is inconsistent among operators. For example, as shown in FIG. 8, a part of the blood cell separating membrane 122 inside the through hole 130 of the film 120 may not be covered with the sample liquid X10 in some cases.
Such problem occurs not only in blood dropping but also when the above-mentioned standard concentration test solution is dropped as a sample liquid to periodically perform calibration.
When the blood cell separating membrane is not sufficiently covered with a sample liquid (liquid to be dropped such as blood, standard concentration test solution or the like), the amount of a liquid that penetrates to the rear surface of the blood cell separating membrane (analysis target liquid of electrode type sensor) becomes insufficient and problems occur in that the sensor head of the electrode type sensor partly fails to contact the analysis target liquid, and an assumed amount of grape sugar cannot be reacted and the like.
After recognizing the problems of dropping failure as mentioned above, when the spot-application region is seen after enlarging as in FIG. 8, it is easy to locate a region in the spot-application region, which is not covered with a sample liquid (non-covered region).
However, in an actual dropping operation, since the diameter of the through hole of the spot-application region is as small as about 4 mm, it is not easy to determine whether a minute non-covered region is present or absent solely by visual observation. In addition, since the dropped blood shows high viscosity, swelling toward the side, a minute non-covered region located in the base part of the dropped blood is sometimes difficult by simply looking into the case opening from above the device.
The problems mentioned above are common to any measuring devices having a constitution for dropping a sample liquid into a small spot-application region (spot-applying), irrespective of the measurement principles such as enzyme electrode method and the like, and the structure of the spot-application region.
An object of the present invention is to suppress the above-mentioned problems, and confer a concentration measuring device with a function enabling easy judgment, by visual observation, of the presence or absence of a non-covered region when a sample liquid is dropped on a spot-application region.